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. 2024 Mar-Apr;21(2):137-143.
doi: 10.21873/cgp.20435.

Association of Androgen Receptor and PD-L1 Expression in Upper Urinary Tract Urothelial Carcinoma

Yohei Okuda  1 , Taigo Kato  2 , Kazutoshi Fujita  3 , Hiroaki Fushimi  4 , Hiroshi Miyamoto  5   6 , George J Netto  7 , Norio Nonomura  1
Affiliations

Association of Androgen Receptor and PD-L1 Expression in Upper Urinary Tract Urothelial Carcinoma

Yohei Okuda et al. Cancer Genomics Proteomics. 2024 Mar-Apr.

Abstract

Background/aim: The response to immune checkpoint inhibitors (ICIs) or enfortumab vedotin is limited in patients with upper urinary tract urothelial carcinoma (UTUC), and the development of new targeted therapy for UTUC is eagerly needed. Several biomarkers, including programmed cell death-ligand 1 (PD-L1), have already been reported as predictors of response to ICIs therapy for UTUC. Recently, several studies have shown that steroid hormone receptors, including the androgen receptor (AR), are associated with progression of urothelial carcinoma.

Materials and methods: We prepared tissue microarrays (TMA) from paraffin blocks of UTUC specimens in 99 non-metastatic UTUC patients who underwent radical nephroureterectomy. With these TMA sections, we performed immunohistochemical staining for PD-L1 and AR and examined PD-L1 and AR expression levels in tumor cells. In addition, we analyzed the correlation between these markers and clinical prognosis in UTUC cases.

Results: PD-L1 was positive in 24 (24%) of the 99 samples, whereas AR was positive in 20 (20%) patients. AR-negative samples had significantly higher PD-L1 expression level than that the AR-positive samples (mean value 4.70% versus 2.55%, p=0.0324). Among AR-positive cases, patients with absence of PD-L1 expression had significantly lower cancer-specific survival (CSS) than that in PD-L1 expression-positive cases (p=0.049), although PD-L1 expression had no significant impact on CSS in AR-negative cases (p=0.920).

Conclusion: Our findings suggest that AR is the promising target for UTUC treatment, especially in PD-L1-negative cases.

Keywords: AR; Androgen receptor; PD-L1; UTUC; programmed cell death ligand 1; upper urinary tract urothelial carcinoma.

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Conflict of interest statement

The Authors declare that they have no conflicts of interest or financial ties related to this study.

Figures

Figure 1
Figure 1. PD-L1 expression by sex, affected side, tumor grade, and age. There was no significant difference of PD-L1 positivity between (A) male and female, (B) renal pelvis and ureter, (C) low and high grade, and (D) age <70 and ≥70.
Figure 2
Figure 2. The positive incidence of androgen receptor expression by affected side renal pelvis or ureter and sex. (A) The positive incidence of androgen receptor (AR) expression in ureteral cancer cells was significantly higher than that in renal pelvis cancer cells (p=0.0445). (B) The positive incidence of AR expression on cancer cells in males tended to be higher than that in females (p=0.0715). Fisher’s exact test was performed to evaluate the association between localization of the primary tumor and the expression status of AR. AR: Androgen receptor.
Figure 3
Figure 3. Correlation of the expression level of androgen receptor and PD-L1 in upper urinary tract urothelial carcinoma. Androgen receptor (AR)-negative patients had significantly higher PD-L1 expression levels (mean value; 4.70%) compared with AR-positive group (mean value; 2.55%) (p=0.0324). AR: Androgen receptor.
Figure 4
Figure 4. Kaplan-Meier curves for cancer-specific survival stratified by the status of androgen receptor and PD-L1 expression. Among patients with androgen receptor (AR)+ tumors, negative PD-L1 expression was significantly associated with shorter cancer specific survival compared to those with positive PD-L1 expression (p=0.0493). On the other hand, PD-L1 expression in patients with AR-tumors had no significant prognostic impact (p=0.920). Differences between the two groups were assessed using the log-rank test. AR: Androgen receptor.
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